Abstract [en]

Introduction Cox2 inhibitors decrease prostaglandin production and therefore influence bone healing especially in unstable long bone models. It is unclear to what extent implant fixation in stable metaphyseal bone is impaired.

Method Male rats numbering 30 and female rats numbering 40 received a stainless steel screw in the metaphyseal bone of the proximal tibia. Half of the rats were treated with 6.4 mg/kg BW parecoxib by continuous release from a subcutaneous mini pump during 7 or 14 days. After treatment, the pull out force, stiffness, and pull out energy of the screw were measured.

Results No effect of parecoxib on the pull out force was found for male rats. In female rats the pull out force was decreased by 16% (P = 0.03) after 7 days treatment with parecoxib. This effect had disappeared after 14 days.

Conclusion Adverse effects of parecoxib on the early phase healing of metaphyseal bone in female rats are small and were not detectable after 14 days. No effect was seen in male rats, possibly due to a faster metabolic elimination of the drug

Abstract [en]

Adverse effects of cyclooxygenase (COX) inhibitors on bone healing have previously been demonstrated in diaphyseal fracture models in animals. In spite of that, they are widely used as postoperative analgesics in orthopaedic surgery. After joint replacement, a bone repair process starts at the interface between bone and cement. If this process is disturbed, the prosthesis may never become rigidly fixed to the bone, leading to migration and with time loosening.

This thesis investigates the effects of a selective COX-2 inhibitor (parecoxib or celecoxib) on bone healing in metaphyseal bone in a rat model and on knee prosthesis migration after total knee replacement, as measured with radiostereometric analysis. Blood loss, postoperative recovery, and the 2-year subjective outcome, were also measured. In addition, a hemoglobin dilution method for blood loss estimation, used in this thesis, was evaluated.

In the first study, pull-out force of a screw inserted in metaphyseal bone of the tibia in rats was only marginally decreased by parecoxib after 7 days but not after 14 days. In the second and third study, celecoxib treatment resulted in less pain postoperatively in conjunction with total knee replacement (TKR), but no effects were seen on blood loss, range of motion, subjective outcome, or prosthesis migration after 2 years.

Comparing the true blood loss of blood donors with the blood loss estimated by the hemoglobin dilution method, this method was found to underestimate the true blood loss. It is therefore not suitable for calculation of the absolute blood loss volume, but may be used for a rough estimate.

In summary, celecoxib and presumably other cyclooxygenase inhibitors seems not likely to increase the risk of prosthesis loosening.